Antihistamines, such as H1 antagonists, are used to treat seasonal allergic rhinitis (SAR); however, antihistamines do not effectively treat nasal congestion, e.g., stuffed or blocked nasal passages. Pseudoephedrine (Ps, a nasal decongestant) is widely used for the treatment of nasal congestion and other related diseases or disorders; however, it does not effectively treat SAR. Therefore, antihistamine/nasal decongestant combinations are frequently used to more effectively treat SAR.
The antihistamine and nasal decongestant can be administered in single or multiple dosage forms. Single dosage unit combination dosage forms containing a combination of Ps with an H1 antagonist, such as loratadine, cetirizine, fexofenadine, terfenadine, acrivastine or astemizole, are known. These combination tablet dosage forms generally provide a rapid release of the antihistamine and a controlled release of Ps. For example, Allegra-D™, Claritin-D™, Claritin-D™ 24-Hour, Seldane-D™ and Semprex-D™ (capsule) dosage forms are commercially available products that provide a rapid release of an H1 antagonist and a controlled or sustained release of Ps. These tablets are generally made for once- or twice-daily administration. U.S. Pat. No. 6,051,585 to Weinstein et al. discloses a combination formulation containing pseudoephedrine, with limited duration of action, and an antihistamine for treating SAR.
Tablets made for twice-daily administration are subject to significant changes in the plasma concentration of the drugs. The fluctuations occur primarily between the sequential and spaced apart administrations of unit doses, for example, toward the latter half of a 12-hour period during which a first twice-daily tablet releases its drug. The plasma concentration fluctuates from minimum to maximum and back again during a 24-hour period during which twice-daily tablets are administered. Moreover, side effects such as heart palpitations and other cardiac anomalies, which are known to occur in certain patients taking pseudoephedrine as a decongestant, are affected by fluctuations in the plasma concentration of pseudoephedrine.
Applicant's note that Hoechst Marion Roussel has attempted unsuccessfully to develop sustained release osmotic device product that provides therapeutic blood plasma levels of PS and FEX over a 24 hour period.
Sussman et al. (J. Allergy Clin. Immunol. (1999 July), 104(1), pp. 100–106) have reported on the evaluation of the twice daily combined administration of fexofenadine and pseudoephedrine using two separate dosage forms: an immediate release form containing 60 mg of FEX and a sustained release form containing 120 mg of PS.
Fexofenadine (terfenadine carboxylate) and derivatives are known for the treatment of SAR. U.S. Pat. No. 4,254,129 to Carr et al., U.S. Pat. Pat. No. 5,375,693 to Woosley et al., U.S. Pat. No. 5,578,610 to D'Ambra, and U.S. Pat. No. 6,037,353 disclose the use of fexofenadine and related compounds in treating SAR.
U.S. Pat. No. 6,039,974 to MacLaren et al. discloses a bi-layered tablet that comprises fexofenadine and pseudoephedrine. They disclose a method for determining the content uniformity of the bilayered tablet. According to them, the preferred particle surface area range for fexofenadine are greater than about 1.0 m2/g, 2–10 m2/g, 2–6 m2/g, or 2–4 m2/g. In order to achieve these particle surface areas, fexofenadine is micronized. With the appropriate particle size, the content uniformity for fexofenadine has a maximum RSD of about 3.5%.
U.S. Pat. No. 6,171,618 to Johnson et al. discloses an osmotic device comprising cetirizine and pseudoephedrine. The pseudoephedrine is released from the core in a controlled manner and the cetirizine is released from an external drug-containing coat in a rapid manner.
Osmotic devices and other tablet formulations are known for their ability to provide a controlled release of a wide range of drugs. Such osmotic devices and other tablet formulations are disclosed in U.S. Pat. No. 4,014,334 to Theeuwes et al., U.S. Pat. No. 4,576,604 to Guittard et al., Argentina Patent No. 234,493, U.S. Pat. No. 4,673,405 to Guittard et al., U.S. Pat. No. 5,558,879 to Chen et al., U.S. Pat. No. 4,810,502 to Ayer et al., U.S. Pat. No. 4,801,461 to Hamel et al., U.S. Pat. No. 5,681,584 to Savastano et al., U.S. Pat. No. 3,845,770, U.S. Pat. No. 4,008,719 to Theeuwes et al., U.S. Pat. No. 4,058,122 to Theeuwes et al., U.S. Pat. No. 4,116,241 to Theeuwes et al., U.S. Pat. No. 4,160,452 to Theeuwes, U.S. Pat. No. 4,256,108 to Theeuwes, and Argentina Patent No. 199,301, the entire disclosures of which are hereby incorporated by reference. In particular, tablet formulations for providing antihistamines are disclosed in U.S. Pat. No. 4,650,807 to Findlay et al., and U.S. Pat. No. 4,501,893 to Findlay et al., the entire disclosures of which are hereby incorporated by reference.
While conventional sustained release dosage forms, such as described above, are effective, osmotic devices such as those described by Faour et al. (U.S. Pat. No. 6,004,582), the entire disclosure of which is hereby incorporated by reference, are particularly advantageous for delivering two different dosage forms from a single osmotic device tablet. While Faour et al. disclose osmotic device formulations comprising slow release pseudoephedrine with rapid release loratadine and slow release pseudoephedrine with rapid release astemizol, they do not disclose osmotic devices that provide the specific formulations, plasma profiles or release profiles for the various different combinations claimed herein, nor osmotic devices having a drug-containing external coat that has been spray coated rather than compression coated onto the device.